3.1. Cancer
A neoplasm, or tumor, is a neoplastic mass resulting from abnormal uncontrolled cell growth, which may cause swelling on the body surface, and which can be benign or malignant. Benign tumors generally remain localized. Malignant tumors are collectively termed cancers. The term "malignant" generally means that the tumor can invade and destroy neighboring body structures and spread to distant sites to cause death (for review, see Robbins and Angell, 1976, Basic Pathology, 2d Ed., W.B. Saunders Co., Philadelphia, pp. 68-122). Treatment options, such as surgery, chemotherapy and radiation treatment, are either ineffective or present serious side effects. Thus, there is a need for development of new drugs for the treatment of cancer.
Kaposi's Sarcoma (KS) is a rare type of cancer, the incidence of which is greatly increased in HIV infected people (Lunardi-Iskandar, Y., et al., 1995, Nature 375:64-68; Friedman-Kien, A. E., et al., 1981, J. Am. Acad. Dermatol. 5:468-473). The tumors appear to be comprised of hyperplastic cells derived from vascular endothelial cells (Nakamura, S., et al., 1988, Science 242:426-430; Ensoli, B., et al, 1989, Science 243:223-226; Salahuddin, S. Z., et al., 1988, Science 242:430-433; Masood, R., et al., 1994, AIDS Res. Hum. Retroviruses 10:969-976; Lunardi-Iskandar, Y., et al., 1995, JNCI 88:450-454). In some cases, neoplastic cells with chromosomal abnormalities are also present in the tumors (Lunardi-Iskandar, Y., et al., 1995, JNCI 87:974-981; Delli-Bovi, P., et al., 1986, Cancer Res. 46:6333-6338; Siegal, B., et al., 1990, Cancer 65:492-498; Yunis, J. J., 1983, Science 221:227-236; Popescu, N. C., et al., 1995, JNCI 88:450-454). Therapies for KS include radiotherapy, .alpha.-interferon and systemic chemotherapy (Chak, L. Y., et al., 1988, J. Clin. Oncol. 6:863-7; Evans, L. M., et al., 1991, J. Immunother. 10:39-50; Kovas, J., et al., 1990, Ann. Intern. Med. 112:812-21; Gelmann, E. D., et al., 1987, Am. J. Med. 82:456-62; Gill, P. S., et al., 1991, Am. J. Med. 90:427-33; Gill, P. S., et al., 1990; Am. J. Clin. Oncol. 13:315-9; Gill, P. S., et al., 1994, AIDS 8:1695-9). However, hematological and non-hematological toxicities limit the prolonged use of chemotherapy and .alpha.-interferon in conjunction with anti-retroviral agents commonly used in the treatment of AIDS (Kovas, J., et al., 1990, Ann. Intern. Med. 112:812-21; Gill, P. S., et al., 1991, Am. J. Med. 90:427-33; Gill, P. S., et al., 1994, AIDS 8:1695-9). Thus, new drugs, preferably drugs compatible with AIDS therapeutics, are needed for the treatment of KS.